A high-resolution hydro-dynamic model for Delaware Bay was developed, validated and applied to hindcast the largely unknown tracers and circultions of the bay, to investigate the roles of these factors in influencing oyster diseases (e.g., the Multinucleated Spheres of unknown origin, MSX), and to inquiry into the future fate of the bay in response to climate change. In the contemporary bay, a negative temperature/salinity correlation was determined to exist under the modern climate via a positive river flow/temperature correlation and a negative river flow/salinity correlation; warm-salty conditions rarely occur, which helps control MSX; a substantial horizontal salinity gradient provides a habitable refuge for oysters. However, according to the sensitivity studies, sea-level rise and warmer surface air may significantly salinize and warm the bay. Intensified river flow cannot reduce the SLR-induced salinization. The new physical environment may be generally unfavorable to oysters if they are related to oyster diseases.